Determination of acyclovir and its metabolite 9-carboxymethoxymethylguanide in human serum by ultra-high-performance liquid chromatography-tandem mass spectrometry.

A simple and rapid ultra-high-performance liquid chromatography coupled with mass spectrometry method was developed for acyclovir and its metabolite 9-carboxymethoxymethylguanine in human serum. After precipitation of serum samples with 0.1% formic acid in acetonitrile/methanol (40:60, v/v), components were separated on a Luna Omega C18 column (1.6 μm; 2.1 × 150 mm) at 40°C. Mobile phase A (2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v) and mobile phase B (2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v) were used for gradient elution. A linear calibration curve was obtained over the range of 0.05-50 mg/L, and the correlation coefficients were better than 0.999. The limit of quantitation was 0.05 mg/L for both analytes. The intra- and interday accuracy and precision at three concentration levels ranged between 1.6 and 13.3%, and recoveries were achieved with a range between 92.2 and 114.2%. This method was developed and validated for the therapeutic monitoring of acyclovir in patients.